A. Analysis of the histopathology of NSCLC subtypes at two Maryland institutions and in Heidelberg, West Germany, indicate that adenocarcinoma is the predominant subtype occurring currently. We have noted an apparent increase in adenocarcinomas arising in the peripheral airways (bronchioloalveolar carcinomas, BAC), and immunostaining for the major surfactant associated protein (SAP 35) confirms these findings. B. We have established and characterized 8 cell lines from human BAC. Ultrastructural, biochemical and molecular genetic studies confirm that these cell lines are derived from the progenitor cells of the peripheral airways. These lines provide unique reagents to study the biology of these tumors and explore new methods to treat them. In addition, they may prove to be a useful commercial source for human surfactant used to treat infants with the respiratory distress syndrome. C. A randomized prospective clinical study of extensive disease SCLC demonstrates that in vitro chemosensitivity testing accurately predicts the clinical response of the patients to initial as well as to secondary therapy. In addition, there may be a modest benefit to administering individualized drug assay based therapy. Our studies indicate that patients predicted to fail conventional initial or individualized secondary therapy may be offered alternative forms of therapy. D. Panels of cell lines of SCLC, NSCLC and colorectal carcinomas are useful reagents to screen putative new phase I and II drugs using the MTT tetrazolium dye assay. E. A detailed study of the mdr 1 gene in tumors and cell lines from untreated and previously treated SCLC and NSCLC patients indicates that expression of this gene is not correlated with clinical or in vitro chemoresistance in lung cancer.